This Program Project brings together, links and interdigitates five projects that cover the range from the initial patterns of energy deposition of ionizing radiation, through the earliest observable biological effects of radiation (DNA strand breaks), through its mutagenic and cytogenetic effects, to the late effects of radiation of concern in radiation protection (oncogenic transformation) and the basic understanding of these events (oncogene identification and the cloning of repair genes). The projects each address the central theme "The Effects of Small Doses of Radiation" from different points of view. The pattern of energy deposition will be measured in simulated volumes of the order of nanometers. DNA strand breaks will be measured by pulsed - field gel electrophoresis, as well as in prematurely - condensed chromosomes. Chromosome aberrations will be measured, using conventional cytogenetic techniques as well as the newer methods of fluorescent in situ hybridization, following irradiation with gamma-rays, neutrons and charged particles. Assays for oncogenic transformation will be used to investigate the inverse dose-rate for radiations of intermediate to high LET, and to assess the oncogenic potential of low doses of photoneutrons generated by medical linacs. The techniques of molecular biology will be used to characterize and sequence dominant transforming genes (oncogenes) activated by radiation and genes involved in repair and in the G2-block resulting from radiation in both yeast and mammalian cells. An underlying theme is the development of the hierarchy of radiation effects, from the physics and chemistry, to the production of DNA strand breaks, to their development as mutational events and chromosomal aberrations, and to their development in terms of cell lethality and oncogenic transformation. A central scientific core project will be responsible for design and coordination of the various experiments aimed towards understanding this hierarchy, and the development of mechanistic models. Elucidation of molecular mechanisms will contribute to an understanding of radiation induced cancer risks at low doses, of which breast cancer from mammography is a prime example.